Subnutrition during gestation and lactation affects testicular development, serum testosterone concentration and androgen receptor expression in myoid cells of mature rats
Patricia Genovese; Emiliano Herrera; Martín Duque; Andrea Fernandez; Alejandro Bielli
Abstract
Keywords
References
Abd El-Meseeh NA, El-Shaarawy EA, AlDomairy AF, Sehly RA. Changes in rat testis morphology and androgen receptor expression around the age of puberty. Ann Anat. 2016;205:37-44.
Agee J, Parsa C, Huntrakoon M. Morphologic response of rat leydig cells to hemicastration. Arch Androl. 1988;20(1):1-9.
Ahmadnia H, Dolati M, Ghanadi A, Rostami MR, Rezayat A. Effect of unilateral iatrogenic testicular torsion on the contralateral testis in rats: prepubertal and postpubertal. Urol J. 2019;16(5):501-5.
Angelopoulou R, Balla M, Lavranos G, Chalikias M, Kitsos C, Baka S, Kittas C. Sertoli cell proliferation in the fetal and neonatal rat testis: a continuous phenomenon? Acta Histochem. 2008;110(4):341-7.
Ashonibare VJ, Akorede BA, Ashonibare PJ, Akhigbe TM, Akhigbe RE. Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions. Front Immunol. 2024;15:1346035.
Berndtson WE, Thompson TL. Changing relationships between testis size, Sertoli cell number and spermatogenesis in Sprague-Dawley rats. J Androl. 1990;11(5):429-35.
Boos A, Meyer W, Schwarz R, Grunert E. Immunohistochemical assessment of oestrogen receptor and progesterone receptor distribution in biopsy samples of the bovine endometrium collected throughout the oestrous cycle. Anim Reprod Sci. 1996;44(1):11-21.
Brown JL, Dahl K, Chakraborty PK. Effects of follicular fluid administration on serum bioactive and immunoreactive FSH concentrations and compensatory testosterone secretion in hemicastrated adult rats. J Androl. 1991;12(4):221-5.
Chang C, Lee SO, Wang R-S, Yeh S, Chang T-M. Androgen Receptor (AR) physiological roles in male and female reproductive systems: lessons learned from AR-knockout mice lacking AR in selective cells. Biol Reprod. 2013;89(1):21.
Cooper CR, Bhatia JK, Muenchen HJ, McLean L, Hayasaka S, Taylor J, Poncza PJ, Pienta KJ. The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines. Clin Exp Metastasis. 2002;19(1):25-33.
Desai M, Hales CN. Role of fetal and infant growth in programming metabolism in later life. Biol Rev Camb Philos Soc. 1997;72(2):329-48.
Escott GM, Rosa LA, Loss ES. Mechanisms of hormonal regulation of Sertoli cell development and proliferation: a key process for spermatogenesis. Curr Mol Pharmacol. 2014;7(2):96-108.
Forgie AJ, Drall KM, Bourque SL, Field CJ, Kozyrskyj AL, Willing BP. The impact of maternal and early life malnutrition on health: a diet-microbe perspective. BMC Med. 2020;18(1):135.
Genovese P, Núñez ME, Pombo C, Bielli A. Undernutrition during foetal and post-natal life affects testicular structure and reduces the number of sertoli cells in the adult rat. Reprod Domest Anim. 2010;45(2):233-6.
Genovese P, Riaño V, Alzugaray S, Pombo C, Bielli A. (2011). Undernutrition from fetal life to puberty, fetal programming and compensatory growth in rat testes. In: Lee JE, editor. Undernutrition: effects, causes and management. 1st ed. New York: Nova Science. Chapter 4, p. 73-86.
Genovese P, Herrera E, Riaño V, Bielli A. Subnutrition effects during pregnancy and lactation on mitosis, apoptosis, and androgen receptor expression in the rat testis. Reprod Domest Anim. 2019;54(3):506-13.
Genovese P, Herrera E, Fernández A, Duque M, Bielli A. Subnutrition in different pregnancy stages affects IGF-1 serum concentration, its receptor expression and testicular morphology in pubertal male rats. Discov Med. 2024;1(27):27.
Gomes WR, Jain SK. Effect of unilateral and bilateral castration and cryptorchidism on serum gonadotrophins in the rat. J Endocrinol. 1976;68(02):191-6.
Griffin DK, Ellis PJ, Dunmore B, Bauer J, Abel MH, Affara NA. Transcriptional profiling of luteinizing hormone receptor-deficient mice before and after testosterone treatment provides insight into the hormonal control of postnatal testicular development and Leydig cell differentiation. Biol Reprod. 2010;82(6):1139-50.
Haro C, Rangel-Zúñiga OA, Alcalá-Díaz JF, Gómez-Delgado F, Pérez-Martínez P, Delgado-Lista J, Quintana-Navarro GM, Landa BB, Navas-Cortés JA, Tena-Sempere M, Clemente JC, López-Miranda J, Pérez-Jiménez F, Camargo A. Intestinal microbiota is influenced by gender and body mass index. PLoS One. 2016;11(5):e0154090.
Hussein SM, El-Fadaly AB, Metawea AG, Khaled BEA. Aging changes of the testis in albino rat: light, electron microscopic, morphometric, immunohistochemical and biochemical study. Folia Morphol. 2020;79(3):503-15.
Johnson L, Petty CS, Neaves WB. A new approach to quantification of spermatogenesis and its application to germinal cell attrition during human spermiogenesis. Biol Reprod. 1981;25(1):217-26.
Lindgren S, Damber JE, Carstensen HC. Compensatory testosterone secretion in unilaterally orchidectomized rats. Life Sci. 1976;18(11):1203-5.
Lv S, Huang J, Luo Y, Wen Y, Chen B, Qiu H, Chen H, Yue T, He L, Feng B, Yu Z, Zhao M, Yang Q, He M, Xiao W, Zou X, Gu C, Lu R. Gut microbiota is involved in maile reproductive function: A review. Front Microbiol. 2024;15:1371667.
Magre S, Jost A. Sertoli cells and testicular differentiation in the rat fetus. J Electron Microsc Tech. 1991;19(2):172-88.
Marcondes FK, Bianchi FJ, Tanno AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol. 2002;62(4A):609-14.
Marshall GR, Plant TM. Puberty occurring either spontaneously or induced precociously in rhesus monkey (Macaca mulatta) is associated with a marked proliferation of Sertoli cells. Biol Reprod. 1996;54(6):1192-9.
Mendis-Handagama SM, Ariyaratne HB. Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod. 2001;65(3):660-71.
Mori H, Christensen AK. Morphometric analysis of Leydig cells in the normal rat testis. J Cell Biol. 1980;84(2):340-54.
O’Hara L, Smith LB. Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab. 2015;29(4):595-605.
Ola MS, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 2011;351(1-2):41-58.
Orth JM, Gunsalus GL, Lamperti AA. Evidence from Sertoli cell- depleted rats indicates that spermatid number in adults depends on numbers of Sertoli cells produced during perinatal development. Endocrinology. 1988;122(3):787-94.
Paul HA, Bomhof MR, Vogel HJ, Reimer RA. Diet induced changes in maternal gut microbiota and metabolic profiles influence programming of offspring obesity risk in rats. Sci Rep. 2016;6(1):20683.
Pedrana G, Viotti H, Lombide P, Cavestany D, Martin G, Vickers M, Sloboda DM. Maternal undernutrition during pregnancy and lactation affects testicular morphology, the stages of spermatogenic cycle, and the testicular IGF-I system in adult offspring. J Dev Orig Health Dis. 2020;11(5):473-83.
Rebourcet D, O’Shaughnessy PJ, Pitetti JL, Monteiro A, O’Hara L, Milne L, Tsai YT, Cruickshanks L, Riethmacher D, Guillou F, Mitchell RT, van’t Hof R, Freeman TC, Nef S, Smith LB. Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis. Development. 2014a;141(10):2139-49.
Rebourcet D, O’Shaughnessy PJ, Monteiro A, Milne L, Cruickshanks L, Jeffrey N, Guillou F, Freeman TC, Mitchell RT, Smith LB. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis. PLoS One. 2014b;9(8):e105687.
Rey RA, Musse M, Venara M, Chemes HE. Ontogeny of the androgen receptor expression in the fetal and postnatal testis: its relevance on Sertoli cell maturation and the onset of adult spermatogenesis. Microsc Res Tech. 2009;72(11):787-95.
Robb GW, Amann RP, Killian GJ. Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil. 1978;54(1):103-7.
Rodríguez-González GL, Reyes-Castro LA, Vega CC, Boeck L, Ibáñez C, Nathanielsz PW, Larrea F, Zambrano E. Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress. Age (Dordr). 2014;36(6):9721.
Russell LD, Peterson RN. Determination of the elongate spermatid-Sertoli cell ratio in various mammals. J Reprod Fertil. 1984;70(2):635-41.
Sanefuji T. Tissue culture studies on compensatory testicular hypertrophy of the young rabbit after hemicastration. Hinyokika Kiyo. 1988;34(4):585-91. PMid:2456677.
Sharpe RM, McKinnell C, Kivlin C, Fisher JS. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction. 2003;125(6):769-84.
Silva VA Jr, Vieira AC, Pinto CF, Paula TA, Palma MB, Amorim MJL, Amorim AA Jr, Manhães-de-Castro R. Neonatal treatment with naxolone increases the population of Sertoli cells and sperm production in adult rats. Reprod Nutr Dev. 2006;46(2):157-66.
Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30:2-13.
Stanley E, Lin CY, Jin S, Liu J, Sottas CM, Ge R, Zirkin BR, Chen H. Identification, proliferation, and differentiation of adult Leydig stem cells. Endocrinology. 2012;153(10):5002-10.
Steinberger A, Steinberger E. Replication pattern of Sertoli cells in maturing rat testis in vivo and in organ culture. Biol Reprod. 1971;4(1):84-7.
Tan KA, De Gendt K, Atanassova N, Walker M, Sharpe RM, Saunders PT, Denolet E, Verhoeven G. The role of androgens in Sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor. Endocrinology. 2005;146(6):2674-83.
Wang RS, Yeh S, Tzeng CR, Chang C. Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocr Rev. 2009;30(2):119-32.
Wen YL, Deng XZ, Yang ZW, Wang AG, Zhang ZP, Wu J, Jiang T, Tang S, Cai YL, Li YX, Fan J. Histological effects of unilateral spermatic cord torsion without removal of the ipsilateral necrotic testis on the contralateral testis in rats. Zhonghua Nan Ke Xue. 2013;19(7):604-11. PMid:23926676.
Wen Q, Wang Y, Tang J, Cheng CY, Liu YX. Sertoli cell Wt1 regulates peritubular myoid cell and fetal leydig cell differentiation during fetal testis development. PLoS One. 2016;11(12):e0167920.
Yang ZW, Wreford NG, Kretser DM. A quantitative study of spermatogenesis in the developing rat testis. Biol Reprod. 1990;43(4):629-35.
You X, Yang W, Li X, Li X, Huang Y, Huang C. Dietary modulationof pubertal timing: gut microbiota-derived SCFAs and neurotransmittersorchestrate hypothalamic maturation via the gut–brain axis. J Endocrinol Invest. 2025;48(10):2229-48.
Zhu LJ, Hardy MP, Inigo IV, Huhtaniemi I, Bardin CW, Moo-Young AJ. Effects of androgen on androgen receptor expression in rat testicular and epididymal cells: a quantitative immunohistochemical study. Biol Reprod. 2000a;63(2):368-76.
Zhu BC, Chiocchio SR, Han J, Cavicchia J. Neural control of the compensatory increase of testosterone in hemicastrated adult male rats. Sheng li xue bao : [Acta physiologica Sinica]. 2000b;52(1):10-6. PMid:11971164.
Submitted date:
08/06/2025
Accepted date:
02/20/2026
